The objective of this program project is the study of the pathophysiology of thrombotic disease. The work of the group is focussed on the interaction of proteolytic enzymes, fibrinogen, and platelets. A major aim is to obtain quantitative information on the roles of different activation and inhibition mechanisms in thrombotic disease. This aim is being approached by developing specific and quantitative tests which reflect the action of thrombin, plasmin, and factor XIIIa on fibrinogen as well as the platelet release reaction. The tests are being applied in both in vitro and in vivo studies. The present application concerns systematic clinical studies. The studies include a prospective study of thromboembolism after neurosurgery, studies in patients with symptomatic thromboembolism, disseminated intravascular coagulation, and peripheral arterial disease.